Uveal melanoma in African Americans: Diagnostic challenges.

Uveal melanoma (UM) is uncommon in African Americans. Owing to its rarity, UM may not be suspected in African Americans leading to delayed diagnosis. In addition, socioeconomic factors may also play a role in delayed diagnosis. Clinical and ultrasonographic features may be atypical due to racial pigmentation, necessitating diagnostic fine needle aspiration biopsy. Herein, we report an illustrative case series of 12 African Americans with UM highlighting clinical features and diagnostic challenges.

Functional assay for assessment of pathogenicity of BAP1 variants.

BACKGROUND: Pathogenic germline variants in BRCA1-Associated Protein 1 (BAP1) cause BAP1 tumor predisposition syndrome (BAP1-TPDS). Carriers run especially a risk of uveal (UM) and cutaneous melanoma, malignant mesothelioma, and clear cell renal carcinoma. Approximately half of increasingly reported BAP1 variants lack accurate classification. Correct interpretation of pathogenicity can improve prognosis of the patients through tumor screening with better understanding of BAP1-TPDS. METHODS: We edited five rare BAP1 variants with differing functional characteristics identified from patients with UM in HAP1 cells using CRISPR-Cas9 and assayed their effect on cell adhesion/spreading (at 4 h) and proliferation (at 48 h), measured as cell index (CI), using xCELLigence real-time analysis system. RESULTS: In BAP1 knockout HAP1 cultures, cell number was half of wild type (WT) cultures at 48 h (p = 0.00021), reaching confluence later, and CI was 78% reduced (p < 0.0001). BAP1-TPDS-associated null variants c.67+1G>T and c.1780_1781insT, and a likely pathogenic missense variant c.281A>G reduced adhesion (all p ≤ 0.015) and proliferation by 74%-83% (all p ≤ 0.032). Another likely pathogenic missense variant c.680G>A reduced both by at least 50% (all p ≤ 0.032), whereas cells edited with likely benign one c.1526C>T grew similarly to WT. CONCLUSIONS: BAP1 is essential for optimal fitness of HAP1 cells. Pathogenic and likely pathogenic BAP1 variants reduced cell fitness, reflected in adhesion/spreading and proliferation properties. Further, moderate effects were quantifiable. Variant modelling in HAP1 with CRISPR-Cas9 enabled functional analysis of coding and non-coding region variants in an endogenous expression system.

Significance of Social Determinants of Health in Tumor Presentation, Hospital Readmission, and Overall Survival in Ocular Oncology.

PURPOSE: To evaluate the association between social determinants of health (SDH) with presentation and outcomes in patients with ocular cancer. METHODS: The National Cancer Database was queried for primary clinical tumor (cT) classifications of T1 to T4 N0M0 uveal melanoma, conjunctival melanoma, or retinoblastoma diagnosed between January 2006 and December 2017. Pearson χ2 analysis assessed differences in SDH-related characteristics between cancer cohorts. Binary logistic regression with adjusted odds ratios (aORs) and multivariate Cox proportional hazards ratios (HRs) with 95% confidence intervals (CIs) were performed. DESIGN: Cross-sectional with a nationally representative sample. RESULTS: Three thousand nine hundred sixty-eight uveal melanoma cases, 352 conjunctival melanoma cases, and 480 retinoblastoma cases were included. Differences in race, primary payer status, income quartile, population density, facility location, Charlson-Deyo comorbidity score, history of malignancy, cT classification at presentation, surgical treatment, radiotherapy, chemotherapy, 30-day readmission, and overall survival (OS) were observed among the cancers. Female sex (aOR 0.819 [95% CI 0.689-0.973]) and top income quartile (aOR 0.691 [95% CI 0.525-0.908]) had decreased likelihood of advanced cT classification at presentation. No insurance (aOR 1.736 [95% CI 1.159-2.601]) and Medicaid primary payer status (aOR 1.875 [95% CI 1.323-2.656]) had increased likelihood of advanced cT classification. Patients in rural areas (aOR 7.157 [95% CI 1.875-27.320]) were more likely to be readmitted within 30 days after initial treatment. Increased age was associated with decreased 5-year OS (HR 1.040 [95% CI 1.033-1.047]). CONCLUSIONS: SDH may influence advanced cT classification at presentation and 30-day readmission compared with OS in patients with ocular cancer, highlighting the need for ophthalmologists and public health efforts to address disparities in SDH.

Assessment of Different Circulating Tumor Cell Platforms for Uveal Melanoma: Potential Impact for Future Routine Clinical Practice.

Liquid biopsy and circulating tumor cell (CTC) screening has gained interest over the last two decades for detecting almost all solid malignancies. To date, the major limitation in terms of the applicability of CTC screening in daily clinical practice is the lack of reproducibility due to the high number of platforms available that use various technologies (e.g., label-dependent versus label-free detection). Only a few studies have compared different CTC platforms. The aim of this study was to compare the efficiency of four commercially available CTC platforms (Vortex (VTX-1), ClearCell FX, ISET, and Cellsearch) for the detection and identification of uveal melanoma cells (OMM 2.3 cell line). Tumor cells were seeded in RPMI medium and venous blood from healthy donors, and then processed similarly using these four platforms. Melan-A immunochemistry was performed to identify tumor cells, except when the Cellsearch device was used (automated identification). The mean overall recovery rates (with mean recovered cells) were 39.2% (19.92), 22.2% (11.31), 8.9% (4.85), and 1.1% (0.20) for the ISET, Vortex (VTX-1), ClearCell FX, and CellSearch platforms, respectively. Although paramount, the recovery rate is not sufficient to assess a CTC platform. Other parameters, such as the purpose for using a platform (diagnosis, genetics, drug sensitivity, or patient-derived xenograft models), reproducibility, purity, user-friendliness, cost-effectiveness, and ergonomics, should also be considered before they can be used in daily clinical practice and are discussed in this article.

Hydrogen nanobubbles: A novel approach toward radio-sensitization agents.

BACKGROUND: Ocular melanoma is a rare kind of eye malignancy that threatens the patient's eyesight. Radiotherapy and surgical removal are the most commonly used therapeutic modalities, and nanomedicine has lately entered this field. Brachytherapy using Ruthenium-106 (106 Ru) ophthalmic plaques has been used for decades to treat ocular melanoma, with the applicator placed on the patient's eyes until the prescribed dose reaches the tumor apex. PURPOSE: To investigate the efficiency of hydrogen nanobubbles (H2 -NBs) employment during intraocular melanoma brachytherapy using a 106 Ru electron emitter plaque. METHODS: The Monte Carlo (MC) simulation and experimental investigation using a 3D-designed phantom and thermoluminescence dosimetry (TLD) were employed. Various concentrations of H2 -NBs with a diameter of 100 nm were simulated inside tumor tissue. The results were presented as deposited energy and dose enhancement factor (DEF). An equivalent Resin phantom of the human eyeball was made using AutoCAD and 3D-Printer technologies. The glass-bead TLDs dosimeter were employed and placed inside the phantom. RESULTS: Using a 1% concentration of H2 -NBs, a DEF of 93% and 98% were achieved at the tumor apex of 10 mm from the experimental setup and MC simulation, respectively. For simulated concentrations of 0.1%, 0.3%, 0.5%, 1%, and 4% H2 -NBs, a maximum dose enhancement of 154%, 174%, 188%, 200%, and 300% were achieved, respectively, and a dose reduction was seen at about 3 mm from the plaque surface. CONCLUSION: H2 -NBs can be used as an absorbed dose enhancer in 106 Ru eye brachytherapy because of their unique physical characteristics. Reducing plaque implantation time on the patient's eye, reducing sclera absorbed dose, and decreasing the risk of patients' healthy organs irradiation are reported as some of the potential benefits of using H2-NBs.

[Doppler ultrasound in the assessment of blood supply to choroidal melanoma: parallels with contrast angiography and histography]. / Ul'trazvukovaya dopplerografiya v otsenke krovosnabzheniya melanomy khorioidei: paralleli s kontrastnoi angiografiei i gistografiei.

PURPOSE: Evaluation of blood supply to choroidal melanoma based on comparison of Doppler characteristics of blood flow with angiographic variant of angioarchitectonics and densitometric parameters of the tumor. MATERIAL AND METHODS: The study was performed in 135 patients (135 eyes) with choroidal melanoma. The initial prominence of the tumors varied from 0.6 to 15.2 mm (mean 5.07±3.58 mm), the diameter of the tumor base varied from 4.1 to 22 mm (mean 10.97±3.62 mm). Taking into account the biometric characteristics of choroidal melanoma, all patients were divided into 3 groups: «small¼ (n=49), «medium¼ (n=34) and «large¼ (n=52). In addition to standard diagnostic examination, the following instrumental methods for assessing the blood supply of choroidal melanoma were carried out: angiography with indocyanine green, optical coherence tomography angiography, ultrasound in color Doppler mapping mode, ultrasound histography. RESULTS: Comparative analysis of Doppler ultrasound and contrast angiography data in assessing the blood supply of choroidal melanoma established that the first angiographic type, presented by straight and parallel vessels (65%, p=0.037), is characteristic for hypovascular and avascular masses, the second type - for hypervascular choroidal melanomas, in which the new vessels can take the form of arches, loops and nets (68%, p=0.027). The study of densitometric characteristics in choroidal melanoma of various sizes indicates a natural decrease in the acoustic density of the tumor tissue with increase in the prominence of the mass, while there are significant differences in the acoustic density values in hypo/avascular (36.53±5.37 dB) and hypervascular variants (29.28±4.53 dB) of blood supply to tumor tissue. CONCLUSION: The obtained data on acoustic density of choroidal melanoma can be used in clinical practice for indirect assessment of the nature of blood supply to choroidal melanoma.

Ensuring equity in the era of HLA-restricted cancer therapeutics.

In January 2022, the US Food and Drug Administration granted regulatory approval to tebentafusp, a bispecific T cell receptor protein that targets melanoma antigen gp100 in the context of the human leucocyte antigen (HLA) A*0201 allele. This approval generated significant excitement, given the relative paucity of effective systemic therapies for advanced uveal melanoma. More broadly, tebentafusp represents the first T cell receptor agent to improve overall survival in any solid tumor.Although HLA-A*02:01 is the most common allele at this locus overall, its expression varies considerably among ethnic groups. It is most frequently expressed in Europeans, and less commonly in African Americans and people of Asian or Pacific Island ancestry. While uveal melanoma is most common in Caucasian populations, other HLA-restricted cancer therapeutics are being developed for indications with more diverse patient populations, such as cervical cancer.We advocate for proactive consideration of the populations eligible for each HLA-restricted therapeutic in development to ensure this emerging therapeutic class does not compound long-standing health disparities. As trials may focus on the most prevalent HLA subtypes, it will take the engagement of multiple stakeholders to ensure equitable access to patients of all ethnic backgrounds.

Fear of prognosis? How anxiety, coping, and expected burden impact the decision to have cytogenetic assessment in uveal melanoma patients.

BACKGROUND: Cytogenetic testing (CGT) in uveal melanoma patients reveals prognostic information about the individual risk of developing distant metastasis with dismal prognosis. There is currently no medical intervention strategy with proven effect on the prognosis, rendering the result of the cytogenetic testing purely informative. We explored patients' socio-demographic backgrounds, psychological preconditions, coping strategies, external influences, and concerns about "knowing their fate" to study their possible interactions with decision-making for CGT. METHODS: Uveal melanoma patients were asked to complete questionnaires on their interest in undergoing CGT for prognostication and the factors influencing their decision. Data were collected on socio-demographics, baseline anxiety (GAD-7), depression (PHQ-9), coping strategies (Brief COPE), and assumed future concerns regarding the CGT result. Data were analyzed by using multiple ordinal logistic regression and exploring estimated marginal effects. RESULTS: Questionnaires were returned by 121 of 131 (92.4%) patients. Fifty-two patients (43%) had no interest in CGT, 34 (28.1%) were undecided, and 35 (28.9%) were interested. We observed no significant differences regarding age, sex, partnership, education, occupation, baseline anxiety, or depression. Decision-making favoring CGT was influenced by the treating physicians, internet resources, and level of baseline anxiety. Patients were likely to reject CGT when they worried that "knowing the result will have an unintended influence" on their life. CONCLUSION: Decision-making about CGT for prognostication in uveal melanoma is burdensome to many patients and in general not guided by medical advice regarding further treatment and screening procedures. The psychological impact of the decision is therefore unique and requires careful support by psycho-oncologists considering the patient's fears and expectations.

Tumour growth rate improves tumour assessment and first-line systemic treatment decision-making for immunotherapy in patients with liver metastatic uveal melanoma.

BACKGROUND: The RECIST-based response variably matches the clinical benefit of systemic therapies for liver metastatic uveal melanoma (LMUM). The aims were to determine whether the tumour growth rate (TGR) can help predict the survival in patients with LMUM and to provide information for the management of first-line systemic treatment. METHODS: This retrospective study included 147 (training: n = 110, validation: n = 37) patients with LMUM treated with first-line systemic treatment between 2010 and 2021. Two TGR-derived parameters were calculated, TGR0 and TGR3m. Multivariate Cox analyses identified independent predictors of progression-free survival (PFS) and overall survival (OS). RESULTS: TGR3m was a strong independent prognostic factor of PFS and OS (p < 0.001). The RECIST-based response was no longer significant in the OS analyses. Only immunotherapy regimens correlated with higher OS (HR = 0.2; 95% CI, 0.1-0.5; p < 0.001) in the low-TGR3m (≤50%/m) subgroup. These findings were confirmed in the validation cohort. TGR0, disease-free interval (DFI), and the sum of target lesions at baseline were predictive factors of low TGR3m. DISCUSSION: The use of TGR3m would improve tumour assessment by identifying patients who would benefit from first-line immunotherapy regimens despite PD. TGR0, DFI and the sum of target lesions were correlated with TGR3m, which can support first-line treatment decision-making for immunotherapy.

Assessment of sorafenib induced changes in tumor perfusion of uveal melanoma metastases with dynamic contrast-enhanced ultrasound (DCE-US).

PURPOSE: Dynamic contrast-enhanced ultrasound (DCE-US) was used to monitor early response to sorafenib therapy in patients with liver metastases from uveal melanoma. METHODS: In total, 21 patients with liver metastases were recruited within a prospective trial and underwent daily sorafenib therapy. DCE-US of a target lesion was performed before initiation of treatment, on day 15 and 56. Two independent blinded investigators performed software analysis for DCE-US parameters and inter-observer-correlation was calculated. Response to treatment was evaluated on day 56. DCE-US parameters were correlated with clinical response and RECIST1.1 criteria. RESULTS: Inter-observer-correlation (r) of DCE-US parameters [time-to-peak (TTP), mean-transit-time (MTT), peak intensity (PI), regional blood volume (RBV), regional blood flow (RBF)] at baseline, day 15, and day 56 was highly significant (r-range 0.73-0.97, all p < 0.001). Out of 17 evaluable patients, 12 patients survived day 56 (clinical responders, cRE), whereas, five patients died before day 56 and were classified as non-responders (cNR). TTP values significantly increased in the cRE group 15 days after initiation of treatment for investigator 1 (p = 0.034) and at day 56 for both investigators (p = 0.028/0.028). MTT had increased significantly in the cRE group on day 56 (p = 0.037/0.022). In the cNR group changes for TTP and MTT remained insignificant. Thus, increase of the DCE-US parameters TTP and MTT are associated with response to treatment and prognosis. CONCLUSION: An increase of TTP and MTT at frequent intervals could serve as a surrogate marker for early response evaluation to anti-angiogenic treatment of metastatic uveal melanoma.

Characterization of the HollandPTC proton therapy beamline dedicated to uveal melanoma treatment and an interinstitutional comparison.

PURPOSE: Eye-dedicated proton therapy (PT) facilities are used to treat malignant intraocular lesions, especially uveal melanoma (UM). The first commercial ocular PT beamline from Varian was installed in the Netherlands. In this work, the conceptual design of the new eyeline is presented. In addition, a comprehensive comparison against five PT centers with dedicated ocular beamlines is performed, and the clinical impact of the identified differences is analyzed. MATERIAL/METHODS: The HollandPTC eyeline was characterized. Four centers in Europe and one in the United States joined the study. All centers use a cyclotron for proton beam generation and an eye-dedicated nozzle. Differences among the chosen ocular beamlines were in the design of the nozzle, nominal energy, and energy spectrum. The following parameters were collected for all centers: technical characteristics and a set of distal, proximal, and lateral region measurements. The measurements were performed with detectors available in-house at each institution. The institutions followed the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice for absolute dose measurement, and the IAEA TRS-398 Code of Practice, its modified version or International Commission on Radiation Units and Measurements Report No. 78 for spread-out Bragg peak normalization. Energy spreads of the pristine Bragg peaks were obtained with Monte Carlo simulations using Geant4. Seven tumor-specific case scenarios were simulated to evaluate the clinical impact among centers: small, medium, and large UM, located either anteriorly, at the equator, or posteriorly within the eye. Differences in the depth dose distributions were calculated. RESULTS: A pristine Bragg peak of HollandPTC eyeline corresponded to the constant energy of 75 MeV (maximal range 3.97 g/cm2 in water) with an energy spread of 1.10 MeV. The pristine Bragg peaks for the five participating centers varied from 62.50 to 104.50 MeV with an energy spread variation between 0.10 and 0.70 MeV. Differences in the average distal fall-offs and lateral penumbrae (LPs) (over the complete set of clinically available beam modulations) among all centers were up to 0.25 g/cm2 , and 0.80 mm, respectively. Average distal fall-offs of the HollandPTC eyeline were 0.20 g/cm2 , and LPs were between 1.50 and 2.15 mm from proximal to distal regions, respectively. Treatment time, around 60 s, was comparable among all centers. The virtual source-to-axis distance of 120 cm at HollandPTC was shorter than for the five participating centers (range: 165-350 cm). Simulated depth dose distributions demonstrated the impact of the different beamline characteristics among institutions. The largest difference was observed for a small UM located at the posterior pole, where a proximal dose between two extreme centers was up to 20%. CONCLUSIONS: HollandPTC eyeline specifications are in accordance with five other ocular PT beamlines. Similar clinical concepts can be applied to expect the same high local tumor control. Dosimetrical properties among the six institutions induce most likely differences in ocular radiation-related toxicities. This interinstitutional comparison could support further research on ocular post-PT complications. Finally, the findings reported in this study could be used to define dosimetrical guidelines for ocular PT to unify the concepts among institutions.

Cost-utility analysis of a decade of liver screening for metastases using the Liverpool Uveal Melanoma Prognosticator Online (LUMPO).

This paper outlines a method for cost-utility analysis of liver screening for metastases in patients with posterior uveal melanoma (UM). A semiparametric model of the cumulative incidence of onset of liver metastases was fitted to a retrospective data set of 615 subjects with clinical follow-up with respect to liver surveillance imaging and outcome. The model was internally validated via bootstrap resampling in terms of its discrimination and calibration performance. Receiver operating characteristics (ROC) were derived at different time points. The discrimination performances are consistent across time. The area under the ROC curve at 5 years post treatment was 0.85 [95% CI: 0.81-0.88]. A goodness-of-fit test gives χ2(10)=5.3,p=0.9 demonstrating no evidence against the null hypothesis of zero difference between observed and expected onset of metastatic events. Results showed that at 80% sensitivity, 87% of UM patients will avoid unnecessary radiological scans. This provides potential cost savings of between £46,000 and £97,000 per year to the National Health Service assuming 600 new cases per year.

Patterns of care and follow-up care of patients with uveal melanoma in German-speaking countries: a multinational survey of the German Dermatologic Cooperative Oncology Group (DeCOG).

PURPOSE: Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting. METHODS: A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated. RESULTS: 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures. CONCLUSION: Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.

Iris melanoma with ciliary body infiltration presenting as a presumed chronic unilateral inflammatory glaucoma. The challenges of iris tumor biopsy assessment.

Uveal melanoma is the most common primary malignancy of the eye in adults. It may involve the choroid and ciliary body, and in only 2-3% of cases it involves the iris. We present a case of a 56-year-old patient with a 6-year history of unilateral, inflammatory, refractory glaucoma of the right eye. Due to acquired heterochromia and heterogeneous thickness of the iris, iris melanoma was suspected, but the incisional biopsy did not confirm the diagnosis. In the next months, the lesion enlarged and the eye globe was enucleated. Histopathological examination revealed an iridociliary melanoma with annular growth pattern.

Assessment of the Chemosensitivity of Uveal Melanoma Cells Ex Vivo.

The study was designed to create a primary cell culture of uveal melanoma and to evaluate its resistance to chemotherapy. Of the obtained 20 samples of uveal melanoma, the primary cultures with proliferation sufficient for MTT test were derived in only 7 cases. However, even these cultures were unable to survive more than 4 passages; the cells accumulated melanin and underwent apoptosis. Retinol palmitate and nepafenac produced no cytotoxic effect on uveal melanoma cells. Of 5 cultures treated with sodium valproate (Convulex), no pronounced cytotoxic effect was observed in one culture (UM4); in 2 cultures, 50% cells died in the presence of the lowest drug concentration of 1.88 mg/ml; and in 2 cultures, the same effect was achieved at drug concentrations 7-10 mg/ml. The cytotoxic effect of treosulfan was evaluated in only 4 cultures of uveal melanoma: the drug exhibited pronounced antitumor activity on all cultures, in 2 cases, it was effective at a concentration of 0.16 mg/ml. Gemcitabine in a concentration of 2.5 mg/ml produced a pronounced cytotoxic effect in 4 out of 7 cultures (death of 70-80% cells) and induced death of ~45% cells in the remaining 3 cultures. Mitoxantrone had ambiguous effect: in 2 of 5 cultures, the drug in high concentrations stimulated the growth of tumor cells, but in 3 cultures, the drug even in minimum concentrations induced death of 70-80% cells.

Cherenkov Luminescence Imaging for Assessment of Radioactive Plaque Position in Brachytherapy of Uveal Melanoma: An In Vivo Feasibility Study.

Purpose: To study the feasibility of using Cherenkov luminescence imaging (CLI) to evaluate and document ruthenium-106 plaque position during brachytherapy of uveal melanoma. Methods: Ruthenium-106 decays by emitting high-energy beta particles. When the electrons pass through the eye, Cherenkov radiation generates a faint light that can be captured by highly sensitive cameras. Patients undergoing ruthenium-106 plaque brachytherapy for posteriorly located choroidal melanoma were examined by CLI, which was performed in complete darkness with an electron multiplying charged-coupled device camera mounted on a fundus camera modified for long exposures. Results: Ten patients with tumors ranging from 5.8 to 13.0 mm in largest basal diameter and 2.0 to 4.6 mm in height were included. The plaques had an activity between 0.035 and 0.089 MBq/mm2 at the time of examination (1-4 days after implantation). CLI revealed the actual plaque position by displaying a circular area of light in the fundus corresponding with the plaque area. The Cherenkov light surrounded the tumor as a halo, which showed some asymmetry when the plaque was slightly displaced. The light intensity correlated positively with plaque activity and negatively with tumor pigmentation. Exposure times between 30 and 60 seconds were required to display the plaque position and delineate the tumor area. The long exposures made it difficult to maintain stable eye fixation and optimal image quality. Conclusions: CLI is a novel method to assess and document ruthenium-106 plaque position in brachytherapy for uveal melanoma. Translational Relevance: Ocular CLI may provide relevant radiation data during and after implantation of radioactive plaques, thus improving the accuracy of episcleral brachytherapy.

Evaluation of Racial, Ethnic, and Socioeconomic Associations With Treatment and Survival in Uveal Melanoma, 2004-2014.

Importance: Identifying disparities in uveal melanoma (UM) treatment patterns and survival across racial, ethnic, and socioeconomic (SES) groups reveals possible inequities in ophthalmologic health care. Objective: To examine the association of race, ethnicity, and SES with UM treatment and survival. Design, Setting, and Participants: A retrospective cohort analysis of 28% of the US population using the Surveillance, Epidemiology, and End Results (SEER) 18 registries from January 1, 2004, to December 31, 2014, was conducted. Data analysis was performed from April to July 2018. SEER identified 4475 individuals using International Classification of Diseases for Oncology, Third Edition site and morphology codes. Exposures: Race, ethnicity, and SES estimated by tertile using Yost Index composite scores. Main Outcomes and Measures: Treatment odds ratios (ORs), 1-year and 5-year survival estimates, mortality hazard ratios (HRs), and Kaplan-Meier survival curves. Hypothesis was formulated before data collection. Results: Multivariate analyses of 4475 individuals (2315 [51.7%] men; non-Hispanic white, 4130 [92.3%]; nonwhite, 345 [7.7%]) showed that patients who were nonwhite (OR, 1.45; 95% CI, 1.12-1.88) and socioeconomically disadvantaged (lower SES: OR, 2.21; 95% CI, 1.82-2.68; middle SES: OR, 1.86; 95% CI, 1.56-2.21) were more likely to receive primary enucleation. No interactions were observed between race/ethnicity, SES, and stage at diagnosis. From 2004 to 2014, rates of primary enucleation decreased across all racial/ethnic and SES groups, but disparities persisted. Socioeconomically disadvantaged patients had lower 5-year all-cause survival rates (lower SES: 69.2%; middle SES: 68.1%; and upper SES: 73.8%), although disease-specific survival did not vary significantly by racial/ethnic or SES strata. Mortality risk was associated with older age at diagnosis (56-68 years: HR, 1.70; 95% CI, 1.44-2.01; ≥69 years: HR, 3.32; 95% CI, 2.85-3.86), advanced stage of UM (stage 2: HR, 1.40; 95% CI, 1.19-1.65; stage 3: HR, 2.26; 95% CI, 1.87-2.73; and stage 4: HR, 10.09; 95% CI, 7.39-13.77), and treatment with primary enucleation (HR, 2.14; 95% CI, 1.88-2.44) with no racial/ethnic or SES variation. Conclusions and Relevance: In this study, SEER data from 2004 to 2014 suggest that nonwhite and socioeconomically disadvantaged patients with UM are more likely to be treated with primary enucleation, although no such variation appears to exist in disease-specific survival. These differences reveal opportunities to address issues regarding treatment choice in UM.